{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:26:43Z","timestamp":1787567203716,"version":"build-2736575974"},"reference-count":92,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Neonatal bacterial meningitis is a leading cause of infant morbidity and mortality, yet the molecular and cellular basis of the leptomeningeal response to infection remains poorly defined. Here, we study a mouse model of neonatal\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    meningitis, combining conditional gene knockouts, leptomeningeal single-nucleus RNA sequencing, and endothelial cell culture to explore the role of Toll-like receptor 4 (TLR4) signaling in the host response to infection. Deletion of\n                    <jats:italic>Tlr4<\/jats:italic>\n                    in non-myeloid cells dramatically reduced the inflammatory response in all leptomeningeal cell types and abrogated the infection-associated increase in vascular permeability. In a brain endothelial cell line (bEnd.3 cells), exposure to\n                    <jats:italic>E. coli<\/jats:italic>\n                    triggered NF-\u03baB activation, selective internalization of Claudin-5, and increased monolayer permeability, responses that were eliminated by\n                    <jats:italic>Tlr4<\/jats:italic>\n                    knockout. RNA-seq showed that TLR4 controls an NF-\u03baB\u2013driven transcriptional program that orchestrates the endothelial response to\n                    <jats:italic>E. coli<\/jats:italic>\n                    . These findings reveal multiple TLR4-dependent host responses to neonatal Gram-negative bacterial meningitis.\n                  <\/jats:p>","DOI":"10.7554\/elife.110458","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T16:30:17Z","timestamp":1770913817000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.110458","source":"Crossref","is-referenced-by-count":0,"title":["TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis"],"prefix":"10.7554","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7153-4670","authenticated-orcid":true,"given":"Philip V","family":"Seegren","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00za53h95","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine","place":["Baltimore, United 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